Teresa Zelinski

Blood group terminology 2004: from the International Society of Blood Transfusion committee on terminology for red cell surface antigens

1 Bristol Institute for Transfusion Sciences, Bristol, UK 2 Growing your Knowledge, Spit Junction, NSW, Australia 3 American Red Cross Blood Services, Los Angeles-Orange Counties Region, Los Angeles, CA, USA 4 Biotechnology Research Centre, Auckland University of Technology, Auckland, New Zealand 5 Regional Blood Transfusion Center, Department of Clinical Immunology, University Hospital, Arhus N, Denmark 6 Department of Pathology, University Hospitals UH-2G332, Ann Arbor, Michigan, USA 7 Reference Laboratory for Immunohematology and Blood Groups, National Blood Services Centre, Tel Hashomer, Israel 8 New York Blood Center, New York, NY, USA 9 Ortho-Clinical Diagnostics, Raritan, NJ, USA 10 Drexel University College of Medicine, Philadelphia, PA, USA 11 Gamma Biologicals Inc (subsidiary of Immunocor Inc), Houston, TX, USA 12 Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, the Netherlands 13 Centre national de Reference pour les Groupes sanguines (CNTS), Paris, France 14 International Blood Group Reference Laboratory, Bristol, UK 15 Finnish Red Cross Blood Transfusion Service, Helsinki, Finland 16 South African National Blood Service, East Coast Region, Pinetown, South Africa 17 Osaka Red Cross Blood Center, Osaka, Japan 18 Blood Bank, Hospital Sirio-Libanes, Sao Paulo, Brazil 19 Rh Laboratory, University of Manitoba, Winnipeg, Manitoba, Canada

Blood Group Terminology 1995: ISBT Working Party on Terminology for Red Cell Surface Antigens

Since the first human blood groups were discovered almost a century ago, many hundreds of new red cell antigens have been identified. Because of the extended time period over which these antigens were discovered, a variety of different terminologies has been introduced. In some cases single capital letters were used (A, B, M, K), in some superscripts distinguished allelic products (Fy’, Fyh), and in some a numerical notation was introduced (Fy3). Some antigens were given different names in different laboratories, based on alternative genetic theories (D and Rho). In 1980 the International Society of Blood Transfusion (ISBT) established a Working Party to devise a genetically based numerical terminology for red cell surface antigens. In 1990 the Working Party published a monograph describing a numerical terminology for 242 red cell antigens [I], and brief updatings followed in 1991 [2] and 1993 [3]. In the 6 years since the 1990 report many amendments to the classification have been necessary: 18 new antigens have been identified and 6 others declared obsolete due to lack of suitable reagents; four new systems have been created (all from existing collections); the Auberger antigens joined the Lutheran system; the Gregory antigens and Jo” joined the Dombrock system; the Wright antigens joined the Diego system. Furthermore, since, 1990, many of the blood group genes have been isolated: of the genes controlling the 23 systems, only four (PI, JK, SC, DO) remain to be cloned. The purpose of this monograph is to describe the ISBT terminology for red cell surface antigens and to tabulate the complete 1995 version of the classification. In addition, an alternative ‘popular’ terminology is suggested in an attempt to reduce the number of different names used in publications on red cell antigens. Much of the information provided in the 1990 monograph [l] is reiterated here so that referral back will not generally be required, but only references after 1990 are provided.

Mutation of a Gene Essential for Ribosome Biogenesis, EMG1, Causes Bowen-Conradi Syndrome

Bowen-Conradi syndrome (BCS) is an autosomal-recessive disorder characterized by severely impaired prenatal and postnatal growth, profound psychomotor retardation, and death in early childhood. Nearly all reported BCS cases have been among Hutterites, with an estimated birth prevalence of 1/355. We previously localized the BCS gene to a 1.9 Mbp interval on human chromosome 12p13.3. The 59 genes in this interval were ranked as candidates for BCS, and 35 of these, including all of the best candidates, were sequenced. We identified variant NM_006331.6:c.400A-->G, p.D86G in the 18S ribosome assembly protein EMG1 as the probable cause of BCS. This mutation segregated with disease, was not found in 414 non-Hutterite alleles, and altered a highly conserved aspartic acid (D) residue. A structural model of human EMG1 suggested that the D86 residue formed a salt bridge with arginine 84 that would be disrupted by the glycine (G) substitution. EMG1 mRNA was detected in all human adult and fetal tissues tested. In BCS patient fibroblasts, EMG1 mRNA levels did not differ from those of normal cells, but EMG1 protein was dramatically reduced in comparison to that of normal controls. In mammalian cells, overexpression of EMG1 harboring the D86G mutation decreased the level of soluble EMG1 protein, and in yeast two-hybrid analysis, the D86G substitution increased interaction between EMG1 subunits. These findings suggested that the D-to-G mutation caused aggregation of EMG1, thereby reducing the level of the protein and causing BCS.

GPSM2 Mutations Cause the Brain Malformations and Hearing Loss in Chudley-McCullough Syndrome

Autosomal-recessive inheritance, severe to profound sensorineural hearing loss, and partial agenesis of the corpus callosum are hallmarks of the clinically well-established Chudley-McCullough syndrome (CMS). Although not always reported in the literature, frontal polymicrogyria and gray matter heterotopia are uniformly present, whereas cerebellar dysplasia, ventriculomegaly, and arachnoid cysts are nearly invariant. Despite these striking brain malformations, individuals with CMS generally do not present with significant neurodevelopmental abnormalities, except for hearing loss. Homozygosity mapping and whole-exome sequencing of DNA from affected individuals in eight families (including the family in the first report of CMS) revealed four molecular variations (two single-base deletions, a nonsense mutation, and a canonical splice-site mutation) in the G protein-signaling modulator 2 gene, GPSM2, that underlie CMS. Mutations in GPSM2 have been previously identified in people with profound congenital nonsyndromic hearing loss (NSHL). Subsequent brain imaging of these individuals revealed frontal polymicrogyria, abnormal corpus callosum, and gray matter heterotopia, consistent with a CMS diagnosis, but no ventriculomegaly. The gene product, GPSM2, is required for orienting the mitotic spindle during cell division in multiple tissues, suggesting that the sensorineural hearing loss and characteristic brain malformations of CMS are due to defects in asymmetric cell divisions during development.

ABCG2 null alleles define the Jr(a-) blood group phenotype

The high-incidence erythrocyte blood group antigen Jra has been known in transfusion medicine for over 40 years. To identify the gene encoding Jra, we performed SNP analysis of genomic DNA from six Jr(a−) individuals. All individuals shared a homozygous region of 397,000 bp at chromosome 4q22.1 that contained the gene ABCG2, and DNA sequence analysis showed that ABCG2 null alleles define the Jr(a−) phenotype.

Terminology for red cell surface antigens

The Working Party met at Makuhari Messe, Japan on 31 March 1996. A few changes to the current classification, documented in Blood Group Terminology 1995 [1], were agreed and these are described below.

Ethanolamine inhibits choline uptake in the isolated hamster heart

The effect of exogenous ethanolamine on phosphatidylcholine biosynthesis in the isolated hamster heart was investigated. Hamster hearts were perfused with [Me-3H]choline in the presence of 0.05-0.5 mM ethanolamine. Incorporation of label into phosphatidylcholine was decreased 26-63% at 0.1-0.5 mM ethanolamine. Similar decreases in the labelling of the metabolites of the CDP-choline pathway were observed at these ethanolamine concentrations. The observed decrease in phosphatidylcholine labelling at 0.1-0.5 mM ethanolamine was attributed to an inhibition of labelled choline uptake by ethanolamine. The inhibitory role of ethanolamine to choline uptake was examined by comparison to hemicholinium-3. Both compounds inhibited choline uptake in a competitive manner. Intracellular choline, phosphocholine and CDP-choline concentrations were not altered under all experimental conditions. It can be concluded that exogenous ethanolamine has no immediate effect on the rate of phosphatidylcholine biosynthesis in the isolated hamster heart. The reduced labelling of phosphatidylcholine in the presence of ethanolamine is a direct result of the reduction of labelled choline taken up by the heart.

International Society of Blood Transfusion working party on terminology for red cell surface antigens

G. L. Daniels (Chair), D. J. Anstee, J. P. Cartron, W. Dahr, A. Fletcher, G. Garratty, S. Henry, J. Jorgensen, W. J. Judd, L. K ornstad, C. Levene, M. Lin, C. Lomas-Francis, A. Lubenko, J. J. Moulds, J. M. Moulds, M. Moulds, M. Overbeeke, M. E. Reid, P. Rouger, M. Scott, P. Sistonen, E. Smart, Y. Tani, S. Wendel & T. Zelinski*

The Low‐Incidence Blood Group Antigen, Wda, Is Associated with the Substitution Val557→ Met in Human Erythrocyte Band 3 (AE1)

The Waldner blood group antigen (Wda) was first identified in members of a Hutterite kindred. Evidence that the gene governing the Waldner polymorphism is located on chromosome 17, and the observation that the antigen is inactivated by chymotrypsin prompted the investigation of a possible association between Wda and band 3. Single Stranded Conformational Polymorphism (SSCP) analysis and DNA sequence analysis of the AE1 gene, from subjects of known Waldner phenotypes, showed a heterozygous mutation leading to the substitution Val557→ Met in the presumptive Wd(a+) heterozygotes. Therefore the Wda blood group antigen is associated with the presence of Met557 on band 3. The Waldner antigen has been assigned to the Diego blood group system with the International Society of Blood Transfusion number DI5.

A novel mutation in KIAA0196: identification of a gene involved in Ritscher–Schinzel/3C syndrome in a First Nations cohort

Background Ritscher–Schinzel syndrome (RSS) is a clinically heterogeneous disorder characterised by distinctive craniofacial features in addition to cerebellar and cardiac anomalies. It has been described in different populations and is presumed to follow autosomal recessive inheritance. In an effort to identify the underlying genetic cause of RSS, affected individuals from a First Nations (FN) community in northern Manitoba, Canada, were enrolled in this study. Methods Homozygosity mapping by SNP array and Sanger sequencing of the candidate genes in a 1Mb interval on chromosome 8q24.13 were performed on genomic DNA from eight FN RSS patients, eight of their parents and five unaffected individuals (control subjects) from this geographic isolate. Results All eight patients were homozygous for a novel splice site mutation in KIAA0196. RNA analysis revealed an approximate eightfold reduction in the relative amount of a KIAA0196 transcript lacking exon 27. A 60% reduction in the amount of strumpellin protein was observed on western blot. Conclusions We have identified a mutation in KIAA0196 as the cause of the form of RSS characterised in our cohort. The ubiquitous expression and highly conserved nature of strumpellin, the product of KIAA0196, is consistent with the complex and multisystem nature of this disorder.